He entered politics through the influence of the Earl of Bedford, working for the Exchequer in Wiltshire before entering Parliament for Calne, Wiltshire in 1614.[5] Despite his Puritanism he gained a good reputation in Parliament, although he was relentless in his campaigning against Roman Catholics. After the dissolution of Parliament in 1621 he was one of those placed under house-arrest in January 1622. In 1624 he changed his seat, representing Tavistock, Devon, for the rest of his career.[6]

In the interval between Parliaments he was treasurer of the Providence Island Company from 1630, linking him to a small, intense group of Puritan opponents to the King.[8]

In the Short Parliament of 13 April to 4 May 1640 he made one of the speeches that led to its dissolution and "appeared to be the most leading man" according to Clarendon. What would become the Long Parliament first met in November 1640—Pym had avoided an accusation of treason and rose to leader of the opposition to the king.[9]

He was notable in defending the powers of Parliament; he initiated the legal attacks on the Earl of Strafford and William Laud,[2] and attacked the operation of the Star Chamber. It is probable that he even used popular supporters to stage riots, attempting to prevent the House of Lords from vetoing the abolition of episcopacy. When control of the army became an issue, concerning the Irish Rebellion from September to October 1641, Pym directed the house's defiance and helped draft the Grand Remonstrance of grievances presented to the King on 1 December 1641. However, many moderate Members of Parliament were alienated by the radical momentum, led by the Puritan opposition to Charles I.[10]

Thus Pym lost the unity of the House of Commons, which had allowed him to oppose the King from a firm platform; previously the King had had to agree to demands because he could not raise an army alone to fight the Irish rebels. Pym was one of Five Members sought for arrest when the King entered the House of Commons on 5 January 1642 but, forewarned, they had already fled, to return to some acclamation a week later.[10] This shows how great an emphasis Charles placed on Pym's leadership of the Puritan opposition group and how closely he was identified with the Parliamentary cause.

When the English Civil War began in 1642, Pym became involved in solving the financial problems of the Parliamentary side, heading the Committee of Safety from 4 July 1642. He was a key organizer of the loans and taxes that Parliament needed to fund its army and fight the King, and he negotiated the Solemn League and Covenant that gained the support of Scottish Presbyterians.[2] These two things laid firm foundations for Parliament's success in 1645–6 because it now had financial and military resources far beyond those of the Royalists. Pym died, probably of cancer, at Derby House on 8 December 1643 and was buried in Westminster Abbey. Following the Restoration of 1660 his remains were exhumed, despoiled and finally re-buried in a common pit.[11]